Our approach was to determine the influence of a single systemic administration of AM281, synthetic cannabinoid structurally similar to SR141716A, on recognition memory in rats.
To assess the ...influence of AM281 on acquisition of information the compound was given intraperitoneally once, at the doses of 0.1, 0.5, 1.0 or 2.0mg/kg, 15min before learning trial (T1) and in order to evaluate its influence on consolidation process AM281 was given at indicated doses, immediately after T1 trial in an object recognition test. Since cannabinoids may alter motor function and affect anxiety, the influence of AM281 on psychomotor activity and anxiety was evaluated in an open-field and elevated plus maze test, respectively.
Administration of AM281 at the doses: 0.1, 0.5 and 1.0mg/kg significantly improved acquisition of information, while 0.1 and 0.5mg/kg of AM281 significantly facilitated consolidation process. Not only did AM281 not affect locomotor and exploratory activity, but also anxiety.
This is the first evidence that AM281 exerts facilitatory effect on recognition memory in rats. This effect seems to be memory specific because no alterations in animals' psychomotor activity and anxiety were observed.
Abstract I.c.v. administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor (DBI), induces anorexigenic and anxiogenic-like actions in rodents. We have ...recently shown that, in goldfish, i.c.v. injection of ODN also reduces food consumption via the metabotropic endozepine receptor. However, there is little information regarding the structure of DBI and the psychophysiological roles of endozepines in fish. Therefore, in the present study, we isolated and cloned a cDNA encoding goldfish DBI. The deduced sequence exhibits high similarity with non-mammalian DBIs, and we investigated the effect of homologous ODN on psychomotor activity in goldfish. i.c.v. injection of synthetic goldfish ODN at 10 pmol/g body weight (BW) stimulated locomotor activity. Since intact goldfish placed in a tank with both black and white background areas prefers the black compartment, we developed a method for measuring the time taken for fish to move from the black to the white area. I.c.v. administration of diazepam (35 and 350 pmol/g BW) decreased, whereas i.c.v. administration of ODN (10 pmol/g BW) or the central-type benzodiazepine receptor inverse agonist FG-7142 (9 pmol/g BW) increased the time taken to move from the black to the white background area. The anxiogenic-like effect of ODN was blocked by the central-type benzodiazepine receptor antagonist flumazenil (100 pmol/g BW), but was not affected by the metabotropic endozepine receptor antagonist cyclo1-8 d -Leu5 octapeptide (100 pmol/g BW). These data indicate that ODN can potently affect locomotor and psychomotor activities in goldfish and that this action is mediated via the central-type benzodiazepine receptor-signaling pathway.
Abstract
Background: Rating scales used to assess the severity of depression e.g. the Hamilton Depression Rating Scale 17-item (HDRS-17) partly rely on the patient's subjective experience and ...reporting. Such subjective measures tend to have low reliability and adding objective measures to complement the assessment of depression severity would be a major step forward. Aims: To investigate correlations between electronic monitoring of psychomotor activity and severity of depression according to HDRS-17. Methods: A total of 36 patients with unipolar disorder (n = 18) or bipolar disorder (n = 18) and 31 healthy control persons aged 18-60 years were included. Psychomotor activity was measured using a combined heart rate and movement sensor device (Actiheart) for 3 consecutive days, 24 h a day. Results: We found that sleeping heart rate (beats/min) correlated with HDRS-17 in both patients with unipolar disorder and bipolar disorder (unadjusted model: B = 0.46, 95% CI 0.037-0.89, P = 0.034). In contrast, correlations between activity energy expenditure (kJ/kg/day), cardio-respiratory fitness (mlO2/min/kg) and HDRS-17 were non-significant. Conclusions: These results suggest that measuring sleeping heart rate in non-experimental daily life could be an objective supplementary method to measure the severity of depression and perhaps indicate presence of insomnia.
High density of cannabinoid receptors type 1 (CB1) in the brain suggests that endocannabinoid system plays an important role in the functioning of the central nervous system. Natural and synthetic ...cannabinoids are known to attenuate learning and memory processes. The adverse effects of cannabinoids are reversed by SR141716A, at first reported to be a selective CB1 receptor antagonist, later shown to possess also inverse agonist properties. The present study was performed in an attempt to determine the influence of different doses of AM251, a member of the same cannabinoid group as SR141716A, on recognition memory evaluated in an object recognition test. Because cannabinoids may alter motor function and affect anxiety, the influence of AM251 on psychomotor activity and anxiety was assessed in an "open-field" test and elevated plus maze, respectively. While the lowest dose of AM251 (1.0 mg/kg) significantly improved recognition memory, higher doses (2.5 mg/kg and 5.0 mg/kg) did not have an influence on it. Moreover, AM251 did not affect anxiety but in the highest dose significantly attenuated psychomotor activity in rats. The main finding of the present study indicates that AM251, at the dose of 1.0 mg/kg, improves recognition memory in rats without alteration of their psychomotor activity and anxiety. The pro-cognitive effect exerted by compounds belonging like AM251 to diarylpyrazole group may be beneficial in therapeutic use of these compounds, especially in patients with cognitive dysfunctions.
OBJECTIVES: To investigate risk factors for self‐reported adverse drug events (ADEs) in a cohort of annually surveyed Iowa Medicare beneficiaries with mobility limitations.
DESIGN: Prospective cohort ...study with baseline and two annual follow‐up questionnaires.
SETTING: Population‐based sample of Iowa Medicare beneficiaries with mobility limitations.
PARTICIPANTS: Members of the cohort with complete follow‐up questionnaires and prescription dispensing data (N=689).
MEASUREMENTS: The questionnaires asked about self‐reported ADEs in the previous 12 months, sociodemographic data, smoking, alcohol use, number of mobility limitations, and history of chronic disease. Pharmacy dispensing records were the source of number and classes of prescription drug use. Linked Medicare claims provided additional comorbidity data.
RESULTS: Of the 689 subjects, 151 (21.9%) reported an ADE, 83% of which resulted in physician contact and 56% of which resulted in discontinuing the medication. Number of different medications dispensed during the prior year was an independent predictor of a self‐reported ADE. Neither age, extent of mobility limitation, nor number of chronic conditions was independently associated with reporting an ADE.
CONCLUSION: Excess ADE risk observed with increasing mobility limitations is mediated through greater medication use.
Evaluation of depression with actigraphy UEDA, Toshiro; MUKAI, Taijiro; HIGASHI, Mutsuhiro ...
Sleep and biological rhythms,
February 2005, Letnik:
3, Številka:
1
Journal Article
Recenzirano
The aim of this study was to compare four time‐zone activity rates over 24 h between melancholy type major depression (MMD) patients and normal subjects using actigraph. Ten patients diagnosed as ...suffering from MMD in the hospital attached to the Kinki University were the subjects of the present investigation. Another age‐matched group of 10 normal healthy subjects with an approximate sex ratio were taken as controls. Subjects were each asked to consistently wear an actigraph on the wrist from the day of admittance to the day of discharge from the hospital, while the control group wore similar actigraphs over a 1‐week period. Immediately after initiation of therapy (initial phase) for MMD (day 2 after admittance), until the relief phase (1 day before discharge), circadian activities were monitored with actigraphs at four time zones over a 24‐h period: 06:00–12:00, 12:00–18:00, 18:00–24:00 and 00:00–06:00 hours. In the control group, similar procedures were followed to obtain parallel data. In the comparison of MMD patients with controls in the initial phase, the activity rates of the MMD group in the 12:00–18:00 hours zone were significantly higher than the control activity rates, and those of the 18:00–24:00 hours zone were lower than the control. When activity rates in the initial phase were compared with the relief phase in MMD patients, those of the initial phase were higher than the relief phase at 12:00–18:00 hours. In the disease‐stage of MMD, activity rates of time‐zones 12:00–18:00 hours are relatively high in affected patients. Based on actigraphy, an objective therapy criterion for assessing MMD may plausibly be established.
Introduction
Strong centrally acting analgesics, including tapentadol prolonged release (PR), have demonstrated efficacy for the management of non-malignant, chronic pain. Maintaining patient ...independence, including the ability to drive safely, is a key goal of long-term analgesic therapy. This multicenter, open-label, phase 3b trial evaluated the effects of tapentadol PR on driving ability.
Methods
This study included patients who had completed previous tapentadol PR trials for severe low back or osteoarthritis pain. After at least 6 weeks of dose stability, patients continued taking tapentadol PR (50–250 mg twice daily) and could take supplemental immediate-release tapentadol 50 mg, except on the day before or day of the driving test (before the test). Pain intensity was assessed using an 11-point numerical rating scale. The Vienna Test System-Traffic Plus was used to assess cognitive and psychomotor function. The key surrogate parameter for driving ability was a global judgment based on 6 battery tests.
Results
Thirty-eight patients enrolled and completed the trial, and 35 patients completed all 6 tests. Pain scores remained unchanged from enrollment to final visit mean (standard deviation) change, –0.2 (1.0). Approximately two-thirds 65.7% (23/35) of patients were classified as fit to drive based on the global judgment of driving-specific ability 34.3% (12/35) not fit to drive. Total daily tapentadol PR dose (>200 vs. ≤200 mg/day) did not affect global judgment of driving ability (
P
= 0.4885). Two adverse events (considered unrelated to study drug) were reported.
Conclusion
Results suggest that most patients receiving a stable dose of tapentadol PR for severe, chronic pain would be able to drive, consistent with earlier studies evaluating stable treatment with strong opioids. Study design limitations and needs for individual patient assessment must be considered in clinical practice.
Patients with diabetes are a high-risk group for cognitive disorders, the exact pattern and the magnitude of this are still unclear. The research to identify the studies was performed in the ...databases Medline, Pubmed, ScienceDirect. Following the analysis of eligibility a number of 9 studies were included in the meta-analysis. Adults with diabetes showed lower performance than control subjects in all cognitive domains. Although the effect sizes of the diabetes on cognitive functions generally oscillate between low and moderate values they should still be considered because they can affect daily activities.
Behavioral sensitization following repeated intermittent cocaine administrations is thought to involve alterations in cocaine regulation of neural activity within the accumbens and caudate brain ...regions. Although Fos immunohistochemistry and c-
fos in situ hybridization have frequently been used to assess changes in cocaine-induced neural activity following prior cocaine exposure, these techniques have rarely been used to examine neural activity in the accumbens of behaviorally sensitized animals. In the present experiment, we compared the ability of increasing doses of cocaine to induce Fos in the accumbens and caudate of rats following a treatment procedure (7 once daily injections of 15 mg/kg of cocaine or the saline vehicle) shown to produce robust and persistent (1 week) locomotor sensitization. In sensitized animals, there was a leftward shift in the dose-response curve for cocaine induction of Fos in the accumbens, but not in the caudate. These results provide the first parametric evidence for sensitization of cocaine-induced Fos expression in the accumbens.
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